Mycobacterium tuberculosis is a large, complex bacterium that causes tuberculosis (TB) disease in humans and other mammals. TB is a highly contagious disease that spreads from person to person by the respiratory route.
There were 9.4 million new TB cases in 2009, including 1.1 million cases among people with HIV and 0.3 million of MDR-TB [WHO Actions For Life—Towards a world free of tuberculosis; World Health Organization: Geneva, Switzerland, 2006]. MDR-TB requires the treatment duration to be extended from six months to at least two years. Worldwide prevalence of extensively drug resistant TB (XDR-TB) is estimated to be 6.6% among MDR M. tuberculosis strains [WHO Actions For Life—Towards a world free of tuberculosis; World Health Organization: Geneva, Switzerland, 2006].
Despite the keen awareness the epidemic has received, the prevalence of MDR—as well as XDR-TB continues to rise [WHO Anti-tuberculosis drug resistance in the world—Report #4. 2008]. The rapid emergence of MDR and XDR tuberculosis strains are difficult or virtually untreatable with current chemotherapies. Such strains pose a major global health threat, especially in developing countries and in countries with increasing prevalence of HIV/AIDS [Koenig, R. Drug-resistant tuberculosis. In South Africa, XDR TB and HIV prove a deadly combination. Science 2008, 319, 894-897].
The majority of people infected with latent TB infection (LTBI) are able to contain the bacilli from causing symptoms and pose no risk of infecting others. With the exception of obvious drug or disease-mediated immune suppression, little is known about what triggers LTBI to progress to active TB disease but once TB is able to circumvent immunological containment, it is considered to have progressed to active TB disease. Children and adults who are malnourished and/or immune-compromised are at increased risk of disease progression. In 2008, TB claimed the lives of 1.82 million people, of which 500,000 occurred among people infected with HIV, making it the leading cause of death for people with HIV [World Health Organization. Global tuberculosis control: a short update to the 2009 report. Geneva, Switzerland: World Health Organization, 2009].
Consequently, there is an urgent need for the development of new anti-TB drugs, preferably with a new mechanism of action.